Biofilms, Methylation & Heavy Metal Detoxification in Lyme Disease Raj Patel, M.D.

Overview Biofilms Gastrointestinal physiology Definition of Biofilms Examples Prevalence Treatment B. Heavy Metals Signs & symptoms Testing Treatment options Methylation in non-responders C. Conclusion Raj Patel, M.D.

Raj Patel, MD Education: Research: Clinical: MS-Rutgers University MD – Robert Wood Johnson Medical School Residency-Family Medicine Post Graduate studies in Autism Spectrum Disorders Research: Ampligen-CFIDS (Hemispherx Pharmaceutical) Clinical: 16+ years clinical experience Active member of Defeat Autism Now (DAN) Active member of International Lyme and Associated Diseases Society (ILADS) Raj Patel, MD Medical Options for Wellness 5050 El Camino Real, #110 Los Altos, CA 94022 650-964-6700 http://www.DrRajPatel.net Raj Patel, MD

B. Biofilms in Lyme Disease 1. GI Physiology: Structure of normal intestinal lining Raj Patel, M.D.

Raj Patel, M.D.

B. Biofilms in Lyme Disease 1. GI Physiology: Structure of intestinal lining in Gluten intolerance Raj Patel, M.D.

Raj Patel, M.D.

B. Biofilms in Lyme Disease 1. GI Physiology Microbial Flora I. One hundred trillion bacteria in gut comprises 500 different species II. Disruption early leads to immune problems, allergies, and autoimmunity later III. Functions: modulates immune system destroys toxins introduced with food suppress growth of pathogenic bacteria production of key vitamins digestion and absorption of carbohydrates prevention of allergies prevention of inflammatory bowel disease Raj Patel, M.D.

B. Biofilms in Lyme Disease 2. Definition a. Community of bacteria and other organisms surrounded by a extracellular polymeric substance (EPS) b. EPS is composed of DNA, protein, and polysaccharides. Its negative charge attracts Ca/Mg/Fe to strengthen it c. Organisms within a biofilm can communicate and exchange genetic material. d. EPS provides resistance to antibiotics requiring 100-1000X higher levels for eradication. “Testing the susceptibility of bacteria in biofilms to antimicrobial agents .” Antimicrobial Agents and Chemo. Nov 1990 e. EPS provides this organisms protection from UV exposure, pH changes, heavy metal toxicity, and phagocytosis. Raj Patel, M.D.

B. Biofilms in Lyme Disease 3. Examples of Biofilms a. Teeth b. Catheters and IV Lines c. Stagnant pools of water, rivers and streams d. Contact lens e. Polluted areas f. Blood (Fry et al) Raj Patel, M.D.

B. Biofilms in Lyme Disease 4. Prevalence of Biofilms a. Autism Spectrum Disorders b. Chronic Lyme Disease c. Chronic Fatigue Immune Dysfunction Syndrome d. Fibromyalgia e. Autoimmune Illness Raj Patel, M.D.

Raj Patel, MD

B. Biofilms in Lyme Disease 3. Examples of Biofilms Raj Patel, M.D.

Raj Patel, MD

Raj Patel, MD

B. Biofilms in Lyme Disease 5. Role of EDTA in Dissolving Biofilm a. EDTA serves to bind and remove the Ca/Mg/Fe holding biofilms together b. Staph biofilms could not be eradicated by Vancomycin or EDTA alone. Together the two agents successfully removed the biofilm (Kim 2005) c. EDTA and Gentamycin are 1000X more effective at killing Pseudomonas than either agent alone. This effect is completely blocked when Ca or Fe are added (Banin 2005) Raj Patel, M.D.

B. Biofilms in Lyme Disease 6. Treatment of Biofilms a. Enzymes b. EDTA c. Antimicrobials Antifungals d. Fiber Brown Algae Modified Citrus Pectin Activated Charcoal Zeolite e. Probiotics Prebiotics (fresh fruit, legumes, chicory, FOS, inulin) Supportive nutrients (slippery elm, okra, NAG, ecklona cava, colostrum) f. Drainage g. GO SLOW Raj Patel, M.D.

B. Heavy Metals 1. Heavy Metals - Hg, Cd, Pb, & Ar are the best studied a. Hg I. Sources: Thimersol (50% Hg by volume) was the preservative in most vaccines until approx 2001. Cumulative dose in vaccines from birth to age 5 years exceeded the EPA guidelines for safety. Large population of older children and young adults have had significant exposure. Study on NYC adult population revealed 24.8% had blood levels at or exceeding 5ug/l, the NY State reportable level. McKelvey W. Environ Health Perspect. 2007 Oct;115(10):1435-41 Seafood, dental amalgams, and industrial output account for the major sources of exposure today. (26,27) WHO. Methyl Mercury. Environmental Health Criteria, vol. 101. Geneva: World Health Organization, 1990 Sallsten G, et.al., J Dent Res 1996; 75: 594–8 Raj Patel, M.D.

Low level chronic exposure can lead to nervous system 1. Heavy Metals (con’t) a. Hg II. Toxicity: Low level chronic exposure can lead to nervous system damage resulting in depression, anxiety & cognitive loss Weiss B, Clarkson TW, Simon W. Environ Health Perspect 2002; 110 (Suppl 5): 851–4 Autoimmunity Hultman, P. et al. The FASEB Journal Nov 1994; 1183-90 Paresthesias, insommnia, cognitive difficulties, neuromuscular changes, headaches and anxiety. http://www.epa.gov/iris/subst/0692.htm Raj Patel, M.D.

I. Sources: Color pigment (dyes & paints) Cigarette smoke 1. Heavy Metals (con’t) b. Cd I. Sources: Color pigment (dyes & paints) Cigarette smoke Ni-Cd batteries Phosphate fertilizers Jarup L et al. Health effects of cadmium exposure—a review of the literature and a risk estimate. Scand J Work Environ Health 1998; 24 (Suppl 1): 1–51 WHO. Cadmium. Environmental Health Criteria, vol. 134. Geneva: World Health Organization, 1992 II. Toxicity: Kidney damage Osteoporosis Cancer Jarup, L. Br. Med. Bull. 68:167-182 (2003) Raj Patel, M.D.

I. Sources: Gasoline (Worldwide major source but not in US) 1. Heavy Metals (con’t) c. Pb I. Sources: Gasoline (Worldwide major source but not in US) Lead in drinking water primarily due to the presence of lead in certain pipes, solder, and fixtures. In kids toys and lead based paints in old homes II. Toxicity: Decreased IQ Memory deterioration Cancer Anemia Peripheral nerve symptoms WHO. Lead. Environmental Health Criteria, vol. 165. Geneva: World Health Organization, 1995 Steenland K, Boffetta P. Am J Ind Med 2000; 38: 295–9 Raj Patel, M.D.

I. Sources: Wood preservative Fish Pesticides/food Industrial exposure 1. Heavy Metals (con’t) d. Ar I. Sources: Wood preservative Fish Pesticides/food Industrial exposure II. Toxicity: Cancer-lung, bladder, & kidney Peripheral neuropathy Anemia GI Effects WHO. Arsenic and Arsenic Compounds. Environmental Health Criteria, vol. 224. Geneva: World Health Organization, 2001 Chilvers DC, Peterson PJ. Global cycling of arsenic. In: Hutchinson TC, Meema KM (eds) Lead, Mercury, Cadmium and Arsenic in the Environment. Chichester: John Wiley & Sons, 1987; 279–303 www.epa.gov/ttn/atw/hlthef/arsenic.html Raj Patel, M.D.

B. Heavy Metals (con’t) 2. Testing for Heavy Metals Blood levels useful for acute exposure, but unreliable tool for chronic low level exposures. Mercury has affinity for fatty tissue. Rarely seen in blood. The half-life of Pb in blood is about one month whereas the half-life in bone is 20-30 years. (35) WHO. Lead. Environmental Health Criteria, vol. 165. Geneva: World Health Organization, 1995 Difficult to accurately assess total body burden. Urinary porphyrins have some utility – currently probably the best clinical test available. Hair Mineral Analysis may be helpful, but show false negative in individuals with compromised detoxification pathways Provocative challenge-involves administering a test dose of a chelator (DMPS, DMSA, or EDTA) and measuring pre- and post- fecal &/or urine for heavy metals. Raj Patel, M.D.

Nutritional support during chelation essential B. Heavy Metals (con’t) 3. Treatment (con’t) Nutritional support during chelation essential I. Gut binding agents-Bentonite Charcoal Cholestyramine II. Mineral replacement-depending on the chelator used, replace minerals aggressively with special attention to Ca & Mg with EDTA and Cu & Zn with DMPS/DMSA III. Antioxidant support-necessary to quench free radicals generated during heavy metal removal. Supplement with A, C, E, Zn, selenium, and reduced glutathione. IV. Hepatic support Raj Patel, M.D.

Options for Detoxification Testing: Urinary porphyrin testing Hair Mineral Analysis (useful if detoxification intact) RBC Analysis (for recent exposure) Fecal/Urinary testing in conjunction with a provoking agent Treatment: DMSA or DMPS EDTA Raj Patel, MD

Methylation involves transfer of methyl group B. Heavy Metals 4. Assess methylation function in non-responders Definition: Methylation involves transfer of methyl group Methylation plays a role in: Neurotransmitter synthesis and breakdown Renal disease Cardiovascular disease Cancer Heavy metal detoxification Anti-viral immune modulation Raj Patel, M.D.

Methylation Cycle 5,10 MTHF Methionine SAM SAH 5 MTHF Homocysteine Mg Zn SAM MSR Methionine Synthase MTHR B12 SAH 5 MTHF Homocysteine Homocysteine P5P CBS Cystathione P5P Cysteine Raj Patel, M.D. Taurine Glutathione

B. Heavy Metals 4. Assess methylation in non-responders (con’t) Impairments in Methylation can be the result of the following: Single Nucleotide Polymorphisms (SNPs): Can impair methylation Commonly found in the general population SNPs involving MTHFR C677T have a 47% incidence among Caucasians Ulrich CM. et al. Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):659-68 Heavy metals at low levels can suppress key enzymes involved in methylation Viruses can impair methylation Munzel and Koschel, Proc. Nat’l. Acad. Sci. (USA) 79(1982) 3692-6 Raj Patel, M.D.

B. Heavy Metals 4. Assess methylation in non-responders (con’t) Testing to assess methylation: genomic testing urine/serum amino acid analysis Nutritional Support to open/bypass areas of impairment: MS/MSR: Methyl B12 / Cyano B12 BHMT: TMG (or DMG) MTHFR: Folic/Folinic acid CBS: P5P/B6 CBS: Reduced Glutathione Raj Patel, M.D.

Glutathione Deficiency Rationale: Studies show low glutathione (critical antioxidant) in Lyme Disease due to heavy metals and presence of multiple infections. Defects in methylation can result in low glutathione. These two factors independently and together result in impaired excretion of mercury and other toxic metals/chemicals. Resulting in a higher body burden Raj Patel, MD

Glutathione Deficiency Recommendations: Testing: Measure level of glutathione (fasting plasma or RBC). Treatment: Oral tabs/caps of glutathione are poorly absorbed (perhaps 15%). Alternatives include liposomal, transdermal or IV glutathione, with or without N-acetyl cysteine. Raj Patel, MD

Raj Patel, MD

Raj Patel, MD

Raj Patel, MD

Raj Patel, MD

Raj Patel, MD

Raj Patel, MD

Raj Patel, MD

C. Conclusion 1. Treatment of gut and systemic biofilms in LD can greatly reduce the reservoir of borrelia and its associated coinfections resulting in a greatly diminished risk of relapse 2. Heavy metals are ubiquitous. They can compromise immune functioning, promote overgrowth of candida as well as dysbiotic flora. Judicial heavy metal detoxification, once the lyme/coinfection load has been reduced or concurrently, with appropriate methylation support as needed, may improve outcome and potentially reduce the likelihood of relapse Raj Patel, M.D.

Raj Patel, MD Medical Options for Wellness 5050 El Camino Real, #110 Los Altos, CA 94022 650-964-6700 http://www.DrRajPatel.net Raj Patel, MD